Platelet Alloimmunization after Transfusion

Background and objectives: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. Materials and methods: We studied the frequency of alloimmunization against platelet antigens in 117 patients who received a single series of blood transfusions. They received mostly saline-adenine-glucose + mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal-antibody-specific immobilization of platelet antigen assay. HLA antibodies were detected by the standard lymphocyte cytotoxicity techniques. Results: We found platelet-specific anti-HPA-5b (anti-Br^a) in 2 cases (1.7%). One antibody was the result of de novo immunization. We detected lymphocytotoxic HLA antibodies in 21 patients (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous immunization. Conclusion: There was a low incidence of platelet-specific antibodies after one series of blood transfusions in this group of patients. This is similar to the results of some previous studies in multiply transfused patients, but not with those of others who found a higher incidence.     

Alloimmunization to RhD by Platelet Transfusions in Autologous Bone Marrow Transplant Recipients

Platelet transfusions from RhD-positive (D-positive) donors are often given to RhD-negative (D-negative) cancer patients. The low observed rate of alloimmunization has been attributed to disease and therapy-related immunosuppression. We have studied the occurrence of alloimmunization in 16 D-negative patients who did not have detectable anti-D prior to autologous bone marrow transplantation for malignant disease. All received D-positive platelets, but no other D-positive blood product. Three patients (19%) developed anti-D at 13, 24 and 83 days, respectively, after first receiving D-positive platelets, and after a total dose of 53, 65 and 119 D-positive platelet unit equivalents, respectively. Two of them also developed anti-C. The 13 patients in whom anti-D was not detected were also heavily transfused with D-positive platelets (mean +/- SD = 136 +/- 82 platelet unit equivalents). In 6 of them, the last recorded antibody screen was less than 3 months after the first D-positive platelets, and may not exclude a primary immune response. Thus, despite profound immunosuppression associated with autologous marrow transplantation, alloimmune responses to D-positive red cells in platelet concentrates can occur in some D-negative recipients.     

An Experimental Model for Preventing Alloimmunization against Platelet Transfusions by Pretreatment with Antibody-Coated Cells

The pretreatment of LEW (RT-1l) rat recipients with antibody-coated BN (RT-1n) blood cells resulted in the suppression of the LEW antibody response against subsequent BN platelet and leukocyte transfusions. Both coating with homologous LEW-anti-BN serum or heterologous rabbit-anti-rat lymphocyte serum was effective. Repeated boosting with uncoated platelets or leukocytes did not abrogate the suppression. The degree of suppression was dependent on the amount of antibody used for cell coating. The induced suppression was also extended to uncoated antigens and unrelated third-party cells. The serum-IgG fraction of pretreated rats was strongly immunosuppressive, suggesting that the mechanism of suppression was related to the induction of a broadly reactive regulatory IgG.     

Platelet Transfusions: Shortened Survival of HL-A-Identical Platelets aud Failure of in vitro Detection of Anti-Platelet Antibodies after Multiple Transfusions

Abstract. In a case of congenital thrombasthenia the survival of transfused platelets was found to be extremely shortened. Although no isoimmune-antibodies could be detected by available immunologic techniques, such antibodies must be postulated as being responsible for the elimination of the donor platelets, since survival of the patient's own platelets is normal. The antibodies do not seem to be directed against an antigen of the HL-A type since the survival time of the thrombocytes from an HL-A-identical sibling is equally shortened.     

Donor Leukocyte Transfusions for Treatment of Leukemic Relapse after Bone Marrow Transplantation

Allogeneic bone marrow transplantation is an effective treatment of leukemia. Intensive chemo- and radiotherapy used for conditioning and T-cells of the graft contribute to the control of leukemia. Animal experiments indicate that transfusion of lymphocytes from the marrow donor convert into complete chimerism without producing graft-versus-host disease, if delayed for two months or more. Transfusion of donor leukocytes (DLT) after marrow transplantation has induced lasting remissions in the majority of patients with chronic myelogenous leukemia (CML) in hematological or cytogenetic relapse, some patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), transformed phase CML and multiple myeloma (MMY). The mechanism of the graft-versus-leukemia reaction is discussed.     

Prevalence of Platelet Transfusion Reactions Before and After Implementation of Leukocyte-Depleted Platelet Concentrates by Filtration

To determine the impact of platelet leukodepletion by filtration on the overall prevalence of reported transfusion reactions associated with platelet concentrates, we audited platelet transfusion reactions after infusion of platelet concentrates reported at University Hospitals of Cleveland over 6 months before (interval 1, July 1, 1989 to December 31, 1989) and after (interval 2, July 1, 1990 to December 31, 1990) implementation of the Pall PL 50 filter on our adult Hematology-Oncology inpatient unit (Division 60). Thirty-two (1.7%) of 1,901 random, pooled platelet transfusion events resulted in blood bank transfusion reaction workups in interval 1, compared to 90 (5.3%) of 1,704 in interval 2 (p<0.001). The Division 60 service accounted for more of our hospital-wide platelet reactions after implementation of the filter in interval 2 (84%) than before filtration in interval 1 (42%), p = 0.002. The prevalence of reaction workups for Division 60 was 0.6% for interval 1, compared to 4.3% for interval 2 (p<0.001). No differences were found between interval 1 and interval 2 for the rate of discontinuation of platelet transfusion (36 vs. 32%, p = 0.14), rate of premedication for platelet transfusion (72 vs. 65%, p = 0.6), percentage of direct antiglobulin test-positive reactions (17 vs. 5.4%, p = 0.09), percentage showing icteric/hemolyzed serum (15 vs. 4.4%, p = 0.09), or reactions believed to be due to red blood cell incompatibility (8.8 vs. 1.1%, p = 0.1). We conclude that the use of expensive platelet filtration devices has not decreased the morbidity of random, pooled platelet transfusions, nor the prevalence of time-consuming blood bank evaluation of platelet transfusion reactions in this setting.     

Low frequency of anti‐D alloimmunization following D+ platelet transfusion: the Anti‐D Alloimmunization after D‐incompatible Platelet Transfusions (ADAPT) study

The reported frequency of D alloimmunization in D? recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5 ± 2%. A primary anti‐D immune response was defined as the detection of anti‐D ≥ 28 d following the first D+ platelet transfusion. Data were collected on 485 D? recipients of D+ platelets in 11 centres between 2010 and 2012. Their median age was 60 (range 2–100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1·44%; 95% CI 0·58–2·97%) recipients had a primary anti‐D response after a median serological follow‐up of 77 d (range: 28–2111). There were no statistically significant differences between the primary anti‐D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood‐derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow‐up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D? males and D? females without childbearing potential after transfusion of D+ platelets.     

Transfusion-Related Acute Lung Injury following Random Donor Platelet Transfusion: A Report of Two Cases

Objectives: Transfusion-related acute lung injury (TRALI) following random donor platelet (RDP) transfusion is a rare complication of transfusion without any well-documented case reported in the English language literature. We describe 2 patients in whom TRALI occurred following RDP transfusion. Methods: Conventional clinical and laboratory methods. Results: Both patients developed acute shortness of breath 30–60 min after completion of RDP transfusion and required mechanical ventilatory support. Chest X-ray (CXR) in both cases revealed bilateral pulmonary infiltrates. Patient 1 required vasopressors for hypotension. Right heart catheterization ruled out fluid overload. Patient 2 remained hemodynamically stable. Both patients improved rapidly with continued respiratory support and were extubated within 48 h. CXR at this time showed clearing of infiltrates. In both cases a granulocyte antibody was identified in the plasma of a platelet donor supporting the diagnosis of TRALI. Conclusions: In suspected cases of TRALI, HLA and granulocyte antibody testing is indicated for the recipients and for donors of implicated components. Implicated donors need not be excluded from the donor pool, but can be used for fractionated plasma and plasma-free components.     

Procoagulant Effect of Incompatible Platelet Transfusions in Alloimmunized Refractory Patients

The clinical effectiveness of platelet transfusion in refractory patients is still a subject of debate. We have evaluated the possible hemostatic effect of platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet counts were less than 20,000/μl. Platelet concentrates were always obtained by apheresis procedures from incompatible donors. The posttransfusion platelet recovery was greater than 15% only in 3 cases. In the first 6 patients, measurements of bleeding time performed immediately before transfusion were in all cases longer than 30 min and did not change significantly 10 and 60 min after platelet transfusions. In all patients, ex vivo perfusion experiments with Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were performed immediately before and 10 and 60 min after transfusion. No difference in platelet deposition onto the subendothelial surface was observed after platelet transfusion. Unexpectedly, the deposition of fibrin on the subendothelial surface was statistically augmented in the posttransfusion studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed statistically significant elevations (p < 0.01) in the posttransfusion samples (31.9±12.6 vs. baseline 5.8±1.7 ng/ml), not justified by TAT levels in the transfused material (2.3±0.17 ng/ml). Transfusion of incompatible platelets to refractory patients may activate coagulation mechanisms in the absence of an increase in peripheral platelet count.     

Immunologic Response of Patients With Acute Leukemia to Platelet Transfusions

Nine leukemic patients in aplasia receivedplatelet concentrates from random donorsover a period of 5 to 32 wk (an average of31 transfusions per patient). All nine developed lymphocytotoxic activity (presumably HL-A antibodies) in their serumagainst cells from a panel of 40 selecteddonors within 20-50 days after transfusions were begun. Lymphocytotoxic activity markedly diminished in the sera ofseven surviving patients over a period of8-24 wk despite continued occasionalplatelet transfusions. When lymphocytotoxic activity was present in the serum ofthese patients, survival of transfusedplatelets was significantly reduced. Sera inwhich lymphocytotoxic activity was detected released endogenous serotonin(26 ± 5% SEM) from washed humanplatelets (but not from dog or rabbit platelets) when incubated at 37°C for 30 min.In contrast, sera from these patients, obtained when lymphocytotoxic activity wasnot detected, released minimal amounts ofserotonin (6 ± 2%) and sera from ninehealthy subjects released none (0 ± 1%).The ability of serum to release serotoninwas abolished, and lymphocytotoxic activity was markedly diminished, after preincubation with allogeneic platelets.

Submitted on August 21, 1972 Revised on February 9, 1973 Accepted on February 16, 1973     

Hypotensive Reactions Associated with Platelet Transfusions and Angiotensin-Converting Enzyme Inhibitors

Background and Objectives: To determine the cause of hypotensive reactions associated with platelet transfusions in coronary artery bypass surgery patients. Materials and Methods: Platelet transfusion reactions that occurred during a 3-month period were retrospectively reviewed. Results: Eighteen transfusion reactions occurred in 16 patients. Sixteen of the reactions were hypotensive, and occurred in 14 patients transfused with platelets through negatively charged bedside leukocyte reduction filters. All 14 patients had received angiotensin-converting enzyme (ACE) inhibitors prior to transfusion. Conclusion: Preliminary findings suggest a new type of transfusion reaction associated with the use of negatively charged leukocyte reduction filters during platelet transfusions to patients on ACE inhibitors.     

Adverse Reactions to Platelet Transfusions Are Reduced by Use of Platelet Concentrates Derived from Buffy Coat

We closely observed 86 transfusions to multitransfused hematologic patients with leukocyte-depleted platelet concentrates (PCs) prepared from buffy coats (BC PCs), filtered either prior to storage (BC1) or after 3–4 days' storage (BC3). The patients were first given, randomly, either BC1 or BC3, and were thereafter used as their own controls by giving them the two BC types alternately. The results were compared with an earlier study on standard platelet-rich plasma (PRP) PCs (46 transfusions to 23 patients) and leukocyte-depleted PRP PCs (23 transfusions to 12 patients). There was no difference in adverse reactions between BC1 and BC3 PCs, but BC PCs caused significantly fewer and milder adverse reactions than PRP PCs. Febrile reactions (FTR) occurred in 4.6%, urticarial skin reactions in 21%, and pulmonary reactions in 0% of BC PC transfusions (17, 29 and 0% of patients). The mean corrected increments (CI) at 16–18 h were higher after BC1 PCs than BC3 PCs (10.3 vs. 8.0, p = 0.046). We conclude that adverse reactions are reduced by use of BC PCs. Prestorage leukocyte depletion may improve platelet increments.     

Management of Fetal Alloimmune Thrombocytopenia by Weekly in utero Platelet Transfusions

Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra-uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments.     

Brief Note: A Chart for the Proportion of Donor Blood in the Body after Repeated Transfusions by Replacement

A chart is presented from which the percentage of donor blood in the patient’s body after any number of substitutions of a fixed quantity of blood canbe read off.

Submitted on December 31, 1959 Accepted on March 22, 1960